In a personal attack on the Prime Minister, Mr Johnson said he had got no "real change" from Brussels which was still intent on building "a country called Europe".
The personal nature of his remarks in a speech in London will further infuriate Downing Street that thought it had an agreement with the London Mayor to stop the personal attacks that dominated the start of the campaign.
But Mr Johnson liberally quoted from Mr Cameron's "Bloomberg" speech in which he laid out what reforms to the EU he wanted in order to recommend a vote to stay.
Mr Johnson said none of these goals had been achieved and accused the Government of "systematic subterfuge" in how it portrayed the nature of Britain's current relationship with the EU.
Comparing the EU to the Italian mafia, he also warned of a campaign of "subterfuge" to hide from the British public constitutional changes which he said were being introduced with the aim of creating "a country called Europe".
The Uxbridge MP - who is the leading figurehead of the Leave campaign - said that the Remain camp relied on the three "wholly bogus" myths that membership of the EU boosts the economy and helps preserve peace and that a desire to quit the 28-nation union is anti-European.
What's the European Parliament ever done for us?
What's the European Parliament ever done for us?
1/5 A cap on the amount of hours an employer can make you work
The Working Time directive provides legal standards to ensure the health and safety of employees in Europe. Among the many rules are a working week of a maximum 48 hours, including overtime, a daily rest period of 11 hours in every 24, a break if a person works for six hours or more, and one day off in every seven. It also includes provisions for paid annual leave of at least four weeks every year
2/5 Helping the people of Britain to avoid smoking
In 2014 MEPs passed the Tobacco Products Directive strengthening existing rules on the manufacture, production and presentation of tobacco products. This includes things like reduced branding, restrictions on products containing flavoured tobacco, health warnings on cigarette packets and provisions for e-cigarettes to ensure they are safe
3/5 Helping you to make the right choices with your food
Thanks to the European Parliament, UK consumers have access to more information than ever about their food and drink. This includes amount of fat, and how much of it is saturated, carbohydrates, sugars, protein and so on. It also includes portion sizes and guideline daily amount information so people can make informed choices about their diet. All facts must be clear and easy to understand
4/5 Two year guarantees and 14-day returns policy for all products
Consumers across the EU have access to a number of rights, from things which are potentially very useful, to things which used to be annoying. For example, shoppers in the UK receive a two-year guarantee on all products, and a 14-day period to change their minds and return a purchase, these things are useful
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5/5 Keeping your air nice and fresh (and safe)
Believe it or not, although the situation is improving, some areas of the UK have appalling air quality. A report by the Royal College of Physicians released on 23 February says 40,000 deaths are caused by outdoor air pollution in the UK every year. Air pollution is linked to a number of illnesses and conditions, from Asthma to diabetes and dementia. The report estimates the costs to British business and the health service add up to £20 billion every year
"I am a child of Europe. I am a liberal cosmopolitan and my family is a genetic UN peacekeeping force," said Mr Johnson, who broke briefly into a German-language rendition of Beethoven's Ode To Joy to prove his point.
"I can read novels in French and I can sing the Ode To Joy in German - and if they keep accusing me of being a Little Englander, I will.
"Both as editor of the Spectator and Mayor of London I have promoted the teaching of modern European languages in our schools. I have dedicated much of my life to the study of the origins of our common European culture and civilization in ancient Greece and Rome.
"So I find it offensive, insulting, irrelevant and positively cretinous to be told - sometimes by people who can barely speak a foreign language - that I belong to a group of small-minded xenophobes; because the truth is it is Brexit that is now the great project of European liberalism, and I am afraid that it is the European Union - for all the high ideals with which it began - that now represents the ancien regime."
Mr Johnson's speech follows the Prime Minister's equally high-profile intervention earlier on the same day.
In what was billed as his most emotive speech so far making the case for Britain remaining in Europe, the Prime Minister evoked the image of “rows of white headstones in lovingly-tended Commonwealth war cemeteries” as evidence of the “price this country has paid” to ensure peace and order in the continent.
"Either we influence Europe, or it influences us,” he said.
“And if things go wrong in Europe, let’s not pretend we can be immune from the consequences.”
Senior Government strategists said the speech was a deliberate attempt by Mr Cameron to “move the remain campaign up a gear” and move the focus away from the economy and on to other areas which they believe will swing support behind a stay vote.
Addressing the supporters of Brexit, Mr Cameron said that throughout history British affairs have been intertwined with the affairs of Europe for “good or ill”.
And he argued that a move to leave the EU now would make the continent and the world an inherently less stable place.
“Can we be so sure that peace and stability on our continent are assured beyond any shadow of doubt?” he asked.
“I would never be so rash as to make that assumption.
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