An initial time-topping effort from Marquez was disallowed because he had exceeded track limits at the final Raccordement corner after running wide on the way.
That came amid a flurry of early changes at the top in which both factory man Andrea Dovizioso and Pramac's Iannone put their Ducatis in front prior to Jorge Lorenzo establishing Yamaha in first with a 1m34.054s.
The loss of Marquez's lap demoted him to ninth for a while, but he restored his superiority with first a 1m33.868s to beat Lorenzo's time, then a 1m33.452s next time around to obliterate the opposition.
Iannone threatened to depose him in the last few minutes, albeit using the extra-soft tyre available to Open class runners while Marquez had set his time on mediums.
The Italian was up on Marquez after three splits, before falling just short of a giant-killing Friday top spot.
Alvaro Bautista jumped up to third with a strong late lap on the Gresini Honda, 0.216s down on Marquez.
It ended up being a muted session for Yamaha on the final timesheets, with Lorenzo and Valentino Rossi back in seventh and 10th. Rossi required a last-gasp improvement to bring himself back into the group guaranteed a Q2 place at present.
Tech 3's Bradley Smith emerged as top Yamaha on his team's home ground in fourth, ahead of the Hondas of Dani Pedrosa and Stefan Bradl.
Scott Redding had the session's only fall, losing his Gresini Honda in a low-side at the end of the back straight. He was unhurt.
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