"We are telling the Americans that the sanction measures they are going to take are their own business," French Foreign Affairs Minister Jean-Yves Le Drian told Friday's Le Parisien newspaper. "But we consider the extraterritoriality of their sanctions unacceptable.
"Europeans shouldn't have to pay for the US pulling out of an agreement to which they [the Americans] themselves contributed."
Economy Minister Bruno Le Maire said on Friday that he would set up financial instruments to "assert European sovereignty" against any US moves.
He has already lobbied US Secretary of the Treasury Steve Mnuchin for exemptions or stays of execution for some French companies, he told Europe 1 radio.
Leading French firms, including oil company Total, Carmaker Renault and pharmaceutical firm Sanofi, started doing business with Iran after the 2015 nuclear deal was signed.
France-based European planemaker Airbus has a contract to supply over 100 planes to the Islamic Republic.
"What do we wish to be?" Le Maire asked rhetorically. "Vassals who obey decisions taken by the United States with our fingers down the side of our trousers? Do we want the United States to be the economic gendarme of the planet?"
Warning that the exchanges between Iran and Israel brought a serious danger of "bigger conflicts", Le Drian called for the revival of a "collective dynamic".
"There is no plan B," he declared. "Plan B is war."
Iran, France, Germany and the UK are to meet in Brussels on Tuesday, the EU has announced.