The Arkéa-Samsic sprinter was caught up in the high-speed big crash on stage 13 and was already battling at the very back of the race on Saturday's medium mountain stage.
On Sunday, the race headed for the high mountains of the Pyrenees and Bouhanni was quickly in trouble. He was dropped during a lively start on an uncategorised climb and, although he regained contact on the descent, he was soon off the back again on the first climb.
As Mark Cavendish (Deceuninck-QuickStep) and the other sprinters remained with the peloton on the drag up, Bouhanni lost contact and was soon alone just in front of the broom wagon. He quickly slipped to 20 minutes behind the front of the race and more than 10 minutes behind the peloton.
With around 3,500m of climbing still to come, that made finishing inside the time limit - usually in the region of 45 minutes down on the stage winner - a near-impossible prospect.
After reaching the intermediate sprint at kilometre 67, Bouhanni climbed off his bike and into his team car.
"He was willing to keep going after his crash two days ago. I'm afraid it's a too hard day for him but he gives everything," his sport director Yvan Ledanois told France Televisions.
The Frenchman had been enjoying a decent Tour, with three podium placings to his name in the sprints.
His exit is a further blow for an Arkéa-Samsic team that has been ravaged by crashes. They lost Warren Barguil to the same stage 13 crash, having already lost Clement Russo, Anthony Delaplace, and Dan McLay.
The French team have three riders left in the race in Nairo Quintana, Connor Swift, and Elie Gesbert.
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