Vos attacked on the final climb of the day with 47 kilometres to go, forming a breakaway alongside Lucinda Brand (Trek-Segafredo), Liane Lippert (Team DSM) and Elise Chabbey (Canyon-SRAM) as a reduced peloton struggled behind them.
The group remained at the front of the course until the finale, where Vos was too strong in the sprint and took the stage ahead of Brand in second, Lippert in third and Chabbey in fourth.
Anna van der Breggen (SD Worx) kept the maglia rosa on the day, maintaining the gap of a minute and 21 seconds on her teammates Ashleigh Moolman-Pasio in second place and Demi Vollering a further 36 seconds behind in third after their dominant Stage 2 performance.
Chabbey was the biggest GC mover of the day as she jumped to fourth, 2 minutes and 36 seconds off van der Breggen.
Vos pointed a finger to the sky after crossing the line, dedicating the win to cyclo-cross rider Jolien Verschueren who died from cancer two days prior.
“Of course, it is incredible to win 29 times, when you still can do your passion and do what you love," Vos said.
"It is so strange to lose Jolien Verschueren this week due to cancer. We are here and we think we suffer, but there is so much more in life.
"I thought about her, and that gave me extra power, I knew how dedicated she was, and I wanted to do a special race for her."
After a relatively subdued start to the stage from Casale Monferrato, attacks started to form on the first climb of the day, as Australian Brodie Chapman (FDJ Nouvelle-Aquitaine Futuroscope) crested the peak of the Lago di Morasco with a 16 second lead on the peloton.
The lead proved to be short-lived though, as Chapman was reeled in by a group with fellow Aussie Grace Brown (Team BikeExchange), Chabbey, Sabrine Stultiens (Liv Racing), Lippert and Brand who were then caught themselves by the peloton shortly after.
Brand and Lippert launched away again on the descent of the Morasco where they were joined by Vos, Chabbey and Mikayla Harvey (Canyon-SRAM) as the climb to Ovada approached.
Harvey was dropped on the climb as the four-strong breakaway built a gap of over four minutes on the peloton, Team SD Worx happy to sit back as none of them threatened van der Breggen in the GC.
With a late headwind eliminating the possibility for any more attacks from behind, it was a battle in the breakaway to the finish as Vos timed her sprint to perfection to speed past the rest and take the stage.
Watch the highlights from the Giro d'Italia Donne on SBS from 3:30pm weekends or 4pm weekdays (July 3-12) or available earlier via SBS On Demand and the Cycling Central website.
