Le Pen, who, according to polls, will reach the final round of the election only to be trounced by independent centrist Emmanuel Macron, hit back: "That's called project fear".
"They used the same argument before the Brexit vote and the election of Donald Trump," she said.
Macron, 39, an ex-banker and former Economy Minister who has never held elected office, chimed in, saying: "Those who were responsible for Brexit, who said everything is possible and it will be wonderful have all scampered off. They have all gone into hiding."
He predicted that Britain would suffer from leaving the EU.
"We're going to start seeing the results (of their departure). Because it's other Conservatives who are going to have to deal with it, and by the way we're going to have to be incredibly rigorous (in negotiating with Britain about its exit by not giving them any undue concessions)," he said.
Le Pen told him to "be a good sport".
"The results in Britain are wonderful. They have unemployment that is lower than it's been for decades. Everyone knows what my view is on the euro and the European Union, which forbids economic patriotism, economic patriotism," she said.
"Unlike you, I propose to have a strong France inside Europe," said Macron.
The pair also clashed on secularism, when Le Pen claimed Macron was in favour of the burkini, the body-covering Islamic garment that was recently the subject of controversy on French beaches.
"I don't need a ventriloquist," he shot back. "You are lying (to voters) by twisting the truth."
Migration and Islam were also flash points. "I want to put an end to legal and illegal immigration," said Le Pen said, linking it to Islamic fundamentalism and an "explosive"security situation in France.
The debate, which also included Socialist hopeful Benoît Hamon and leftist firebrand Jean-Luc Mélenchon, covered a wide range of topics, including the economy and foreign policy.
Another six minor candidates were not invited to speak on private channel TF1, to their fury, having to make do with a parallel internet debate.
The consensus was that Macron, who pledges to modernise France with a "neither left nor right" approach, had the most to lose.
While favourite, polls suggest millions of French voters remain unsure the former banker's hands are safe enough to take on what is often dubbed the most powerful job, constitutionally speaking, in the Western world.
He sought to reassure from the outset by saying: "The traditional parties, those who have for decades failed to solve yesterday's problems, won't be able to do it tomorrow either."
Le Pen hopes the debates will break the glass ceiling in polls currently predicting she stands virtually no chance of clinching the presidency.
A Kantar Sofres-Onepoint poll out today put Le Pen level pegging with Macron on 26 per cent in round one, but with him then trouncing her in the run-off on around 60 per cent.
However, with half of French voters saying they are still undecided and a third currently intending to abstain, the stakes are high and on-air slips could radically change the pecking order.
Once favourite but now trailing on 17 per cent, Fillon, 63, is desperate to turn the page on the disclosure that he used almost €1 million of taxpayers' money to employ his wife and children, and suspicions he broke rules on donations by accepting a gift of two suits worth a total of €13,000.
