In Bernal's absence, Slovenian Tadej Pogacar of Team UAE Emirates won back-to-back Tour de France titles and is now considered the man to beat.
Overall leader Primoz Roglic retains the red jersey with just two days left including Sunday's individual time-trial, a discipline in which he is Olympic champion.
On Friday, Pogacar was given the seal of approval from the man widely considered the greatest in the sport, the now 77-year-old Eddy Merckx, known as the 'Cannibal' because of his relentless hunger.
Tour de France: Geraint Thomas finishes 41 seconds behind lead at 20th position in thrilling second stage finale
As Tour rookie Mathieu van der Poel scored a memorable triumph in blistering gung-ho style, Thomas was unable to keep up over the final kilometre.
Bernal completed the 30.3-kilometer (18.8-mile) route in 35 minutes, 41 seconds to clinch overall victory by 1:29, the biggest margin of victory at the Giro since 2015
Giro d'Italia 2021: Britain's Simon Yates wins 19th stage, Egan Bernal stays strong atop leaderboard
Colombian Bernal, the 2019 Tour de France champion, finished third on the day to keep hold of the leaders' pink jersey with only two stages remaining.
Bettiol hunted down Frenchman Remi Cavagna of Deceuninck who had escaped from a big breakaway group with 26 kilometres to go and finished 15 seconds ahead of fellow Italian Simone Consonni.
Martin, 34, resisted his rivals superbly on the final climb, over 11.2km with an average gradient at 9.8 percent, after the 193km ride between Canazei and a summit finish at Sega di Ala in the north of Italy.
The Colombian star, who won the Tour de France in 2019, leads Italian Damiano Caruso by two minutes and 24 seconds with five stages of the Giro remaining.
Giro d'Italia 2021: Lorenzo Fortunato climbs to victory in 14th stage, Egan Bernal holds on to leader's jersey
Colombian Egan Bernal of Ineos was the first of the favourites to cross the finish line to consolidate his hold on the leader's pink jersey.
Giro d'Italia: Andrea Vendrame sees off Chris Hamilton to take 12th stage, Egan Bernal retains overall lead
Vendrame finished ahead of Australia's Chris Hamilton, his final breakaway companion, followed by New Zealand's George Bennett and Italy's Gianluca Brambilla after the 212km run from Siena in Tuscany to Bagno di Romagna.
Team Qhubeka's Schmid won the 162km stage as part of a long-range breakaway while the 2019 Tour de France winner Bernal extended his overall lead in Tuscany.
The Ineos leader and winner of the 2019 Tour de France pulled away from a select group on a gravel ski slope above the clouds with the other overall contenders only able to watch as he skipped away.
Maeder, who rides for Team Bahrain Victorious, was part of a quartet leading the race up the summit finish and the 24-year-old attacked with three kilometres remaining to cross the line 12 seconds ahead of his fellow escapees.
Winner of the 2018 Tour de France, Thomas' overall race ambitions were left in tatters after a fall on Monday saw him lose more than 11 minutes at the arrival at Mount Etna in Sicily.
Roglic leads Pogacar by 57 seconds with Friday's stage 19 and the culminating run up the Champs-Elysees on Sunday both set to be decided in a mass bunch sprint.
Egan Bernal has withdrawn from the Tour de France, his Ineos team said on Wednesday, after the young Colombian fell out of contention and complained of back trouble.
Lennard Kamna won the roller-coaster Stage 16 featuring five categorised climbs after pulling clear of a group of breakaway riders as the race entered the Alps on Tuesday.
Last year's winner Bernal dropped off the lead group on the long Grand Colombier climb and appeared to lose his chance of retaining the title as he dropped to 13th overall, 8 minutes 25 seconds off the yellow jersey.
Tour de France: Soren Kragh Andersen claims victory in Stage 14 as Primoz Roglic clings on to yellow jersey
After two sharp climbs and several attacks in the last 10 kilometers, Andersen broke away with three kilometres left to finish 15 seconds ahead of the chasing pack.