Fillon, 63, has faced protests in recent weeks since he was charged over accusations he gave his wife a fake parliamentary job for which she was paid hundreds of thousands of euros.
The former prime minister was making his way to the stage in a hall in the eastern city of Strasbourg when a shaven-headed man in a T-shirt bearing the slogan "Students for Fillon" emptied a packet of flour on his face and down his suit.
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Six ways Fillon's woes have shaken up France's election
Security guards wrestled the man to the floor and one of the guards tore off the T-shirt.
From the podium, Fillon told the rally he was "the target of merciless persecution".
"They're doing everything they can to discourage me," he said. "But, my friends, what doesn't kill you makes you stronger."
Fillon has claimed his leftwing opponents are behind the accusations against him, which first emerged in the Canard Enchaine newspaper in January.
Previously the frontrunner in the presidential race, Fillon is now languishing at 19 percent in the polls.
French presidential candidate Marine Le Pen has promised to bring back a singular French currency. Source: AP
More on the presidential race
A new poll of voter intentions by the Elabe survey group showed independent centrist Emmanuel Macron and far-right leader Marine Le Pen still out in front before the first round on April 23, but both lost some momentum.
Macron was at 23.5 percent, down two points over a week, and at the same level as Le Pen, who lost half a point.
Scandal-hit Republicans party candidate Fillon was projected at 19 percent, up a point, while hard-left candidate Jean-Luc Melenchon continued his late surge, gaining two points to 17 percent.
Melenchon meanwhile topped Elabe's latest popularity survey, with 51 percent of respondents saying they had a positive view of him.
Macron is second with a 44 percent standing, while Fillon scored 23 percent.
Macron at the beach?
The sister of far-right leader Marine Le Pen was acid-tongued about Macron's performance during Tuesday night's debate.
Macron, a former economy minister and investment banker, is bidding to be the youngest president in modern French history at the age of 39.
"He looked like a little boy with his bucket and spade," Marie-Caroline Le Pen told the Parisien newspaper on Thursday.
