Speaking in Cyprus, Macron said: "As the European Council in December clearly indicated, the Withdrawal Agreement negotiated between the UK and EU is the best agreement possible.
"It is not renegotiable."
Macron called on Theresa May to present the EU's chief negotiator Michel Barnier with her next steps for avoiding a no-deal Brexit on March 29, which he said "no-one wants, but ... we must all, despite everything, prepare for".
May spoke to EU Commission President Jean-Claude Juncker this morning before vowing to her Brexiteer rebels she would push for a renegotiation.
He is thought to have repeated the EU position there would be no renegotiation.
In a statement issued following the outcome of tonight's Westminster votes the Irish government said: "The EU position on the Withdrawal Agreement, including the backstop, is set out in the conclusions of the December meeting of the European Council. It has not changed.
"The Withdrawal Agreement is not open for re-negotiation."
Earlier Manfred Weber, a senior MEP tipped to succeed Juncker as European commission president, suggested Spain could make a new grab for Gibraltar and the £39billion divorce bill could be pushed up.
May has said the deal must be re-written if she has any hope of overturning the 230-vote drubbing MPs inflicted on it two weeks ago.
Weber's warning comes a day after EU negotiator Michel Barnier's deputy Sabine Weyand warned the deal could not be re-opened at all.
Weber, who heads the biggest group in the European Parliament, said the existing deal is a "compromise between many interests".
Weber said: "If there is now a unilateral attempt to reopen the agreement, the consequence will be that not just the backstop has to be renegotiated - then the Gibraltar question, the question of how much money Britain has to pay for exiting, the question of citizens' rights will have to be renegotiated."
Weber, the German leader of the European People's Party, added: "If we reopen (it), then everything will be reopened.
"And to be honest, I don't see much sense in that."
He said what is needed from Britain is "clear orientation" on the two sides' long-term relationship.
Yesterday, Weyand said the British government needed to change position if there was to be a deal in time for exit day on March 29.
The German diplomat, who has been the deputy to Barnier during the Brexit negotiations, said Brussels had a 'margin' for movement on the political declaration about the future trade deal.
But speaking at a conference in Brussels she said the divorce deal was locked and there would be 'no more negotiations' - ruling out a time limit on the backstop demanded by Tory Brexiteer MPs.
She said the negotiation was 'finished' and dismissed calls for changes to the Irish backstop as 'like Groundhog Day'.
The intervention is a fresh blow to Theresa May's hopes of salvaging her deal following the 230-vote drubbing two weeks ago. Downing Street said today the deal had to 'change' if it were ever to be agreed by MPs.
