Speaking after a meeting with North Atlantic Treaty Organisation secretary general Jens Stoltenberg, Macron said that Assad's comments were "unacceptable" because France's priority is "the war against Daesh", using an Arabic term for the group.
In a televised interview Sunday, Macron called Assad "an enemy of the Syrian people" who should ultimately face a war crimes court.
The Syrian president, Bashar al-Assad, in new statements, has accused of treason anyone who works under the leadership of any foreign country.
The French president also promised "initiatives" early next year, and despite being a leading backer of the Syrian opposition, has declared that the departure of Assad was not a pre-condition for talks.
After a string of strong comments by French officials blaming Assad's government for atrocities and failed talks, Assad said on Monday France was supporting bloodshed in Syria, making it unfit to talk about peace settlements.
French Foreign Minister Jean-Yves Le Drian stressed France's role from the early days of the worldwide coalition against the Islamic State.
Assad's fate has been the stumbling block to progress in every round of UN-backed indirect negotiations in Geneva so far between his representatives and those of the Syrian opposition.
On Sunday, French President Emmanuel Macron called Assad "an enemy of the Syrian people" who "will have to respond to his crimes before his people, before the worldwide courts".
In a broadcast interview with France 2 network on Sunday, Macron said that by "mid-to-late February", the anti-IS coalition will have won the war in Syria, recalling that on December 9, Iraqi Prime Minister Haider al-Abadi had announced the end of the war and the victory over the jihadist group.
France on Friday said the Syrian government was doing nothing to reach a peace agreement after nearly seven years of war and said it was committing mass crimes in the Eastern Ghouta region where 400,000 people are besieged by government forces.
"When you have spent your days massacring your people, you should be generally a little more discrete", Le Drian said.