“My view is… that he will get rid of this deal on his own, for domestic reasons,” Mr Macron said at the end of a three-day state visit to the US.
Mr Trump has until 12 May to decide on the deal, which aimed to prevent Iran acquiring nuclear weapons.
He has been a strong critic of the accord, calling it “insane”.
On Wednesday, Mr Macron used similar language to describe frequent shifts in the US position on global issues, including climate change and the Iran agreement.
“It can work in the short term, but it’s very insane in the medium to long term,” he is quoted as telling reporters following a question and answer session with students at George Washington University.
Under the terms of the agreement, reached under Mr Trump’s predecessor Barack Obama, Iran agreed to limit its controversial nuclear programme in return for an easing of economic sanctions.
Mr Macron made changing the US president’s mind on Iran a top priority for his visit but ended up admitting there was a “big risk” Mr Trump would abandon the deal.
He agreed with Mr Trump that any deal should include a wider agreement on Iran’s influence in the Middle East and should cover the country’s nuclear activities longer term, as well as its ballistic missile programme.
He said he would work with Mr Trump to build a “new framework” in the Middle East – and especially in Syria.
His comments came at the end of a state visit in which the two leaders discussed differences on global trade and the environment, including the possibility of the US rejoining the Paris climate accord.
Earlier on Wednesday, Mr Macron used a speech to the joint houses of the US Congress to denounce nationalism and isolationism, in what was seen as a thinly-veiled attack on Mr Trump’s America First agenda.
Warning of “big problems” if Iran resumed its nuclear programme, Mr Trump on Tuesday said a “bigger” deal was possible but it must be built on “solid” foundations.
The current deal, he said, was “insane”. “They should have made a deal that covered Yemen, that covered Syria, that covered other parts of the Middle East,” he said.
The US president has long complained that the accord – signed by the US, Iran, Russia, China, France, the UK and Germany – does nothing to halt Iran’s support for militant groups in the region such as the Lebanese Shia Muslim group Hezbollah.
Mr Trump is also demanding that signatories to the pact agree permanent restrictions on uranium enrichment, a key part of any nuclear programme. Under the current deal these restrictions are set to expire in 2025.
In January, he signed a waiver suspending US sanctions on Iran for 120 days, saying this was the last time he would extend the sanctions relief. The next waiver is due to be signed on 12 May.
Echoing Mr Trump’s concern over Iran’s influence in the region, Gen Joseph Votel, head of the US military’s Central Command, on Thursday described the country as the biggest long-term threat to security in the Middle East.
“[Iran’s] very aggressive approach to the region in trying to spread their revolutionary rhetoric and regime focus here is I think very, very evident”, he told the BBC.
Iranian President Hassan Riuhani has said the US and French leaders have no “right” to renegotiate a seven-party agreement.
Iran would take “important steps regarding our nuclear technology”, he said on Wednesday, but added that the measures would be “peaceful”.
Meanwhile Iran’s Supreme Leader, Ayatollah Ali Khamenei, called on Muslim nations to unite against the US.
He said his country had “successfully resisted bullying attempts” by the US and would continue to do so.