The 35-year-old pushed home favourite Celine Boutier all the way to the end before she eventually prevailed in the Lacoste Ladies Open de France at Golf Club du Medoc.
But it took a birdie at the last from 20 feet for Boutier, a member of the last two triumphant European Solheim Cup teams, to pip Henry by a shot in the 54-hole title battle.
It was Henry’s second top three finish on the tour this year after she tied for third at the Big Green Egg Open in the Netherlands in June.
But that was her first top three finish since the 2015 Turkish Open.
Henry was chasing her third Ladies European Tour title, having won two tournaments back in 2014.
But despite coming so close she was delighted with her efforts which earned her a cheque for around £23,000.
“I’m really happy with how I played,” said the Scot, who had just one bogey in her last 36 holes.
“I feel like I hit a lot of good shots on the back nine, but I just didn’t manage to make any birdies.
Second place isn’t what you dream of, but I’m still really happy because it is a good result and I’m happy to be back in contention.
“I didn’t make any bogeys so I’m really happy with that because it shows that it was really solid golf,” she added.
“I gave it my best but that putt on the last from Celine was outstanding - and that’s why she’s a Solheim Cup player, she was brilliant.”
Henry began the final day one of three players on seven under par, one shot behind lone leader Boutier, after following a solid opening round of 70 with a six-under par 65.
The two players were neck and neck for much of the final day.
Boutier got off to blistering start with birdies at three of the first seven holes, but Henry birdied the second, seventh and ninth to stay just one behind at the turn.
Back to back Boutier bogeys saw the pendulum sway the Glaswegian’s way but another birdie at the 14th left them level.
They were still tied heading down the 18th tied on 10 under. But with Henry lying short with her second shot on the final hole, Boutier made it to the green in two, before rolling in a 20-foot putt with her third shot.