The 24-year-old finished with 52, his third successive half-century and seventh in his last 10 matches.
When McBrine departed in the 31st over, the 28-year-old all-rounder had taken Ireland to 152-3, helping his team recover from losing opener William Porterfield to the first ball of the innings to Alzarri Joseph.
McBrine's second career half-century ended with a lazy swipe to Odean Smith which was gobbled up by Shai Hope behind the stumps.
However, Ireland, who were missing several players including regular captain Andy Balbirnie because of Covid, still had to endure a nervy finish, quickly slipping from 190-4 to 208-8 before Craig Young steered the winning boundary with 31 balls to spare.
It was a memorable series for McBrine -- he also suffered concussion after being hit on the head in the first game.
After West Indies were put in, he claimed 4-28 from his 10 overs of off-spin.
The home side were 119-7 at one stage before former skipper Jason Holder (44) and Akeal Hosein (23) repaired some of the damage.
Hope top-scored with 53 off 39 balls, hitting nine fours and one six as he dominated an opening stand of 72 in 11 overs with Justin Greaves.
McBrine particularly shone when he removed Nicholas Pooran, Shamarh Brooks and skipper Kieron Pollard in quick succession to put Ireland within touch of a famous series victory.
West Indies won the first game by 24 runs before Ireland levelled the series with a five-wicket victory.
The matches form part of the qualifying path for the 2023 World Cup.
West Indies 212 all out in 44.4 overs (Shai Hope 53, Jason Holder 44; Andy McBrine 4-28)
Ireland 214-8 in 44.5 overs (Andy McBrine 59, Harry Tector 52)
Result: Ireland won by two wickets
Series: Ireland 2-1