Adil Rashid became the first England spinner to reach 150 one-day worldwide wickets while Ireland were grateful for a second successive fifty from Curtis Campher to reach a respectable total at the Ageas Bowl.
Earlier, winning the toss and batting first, Ireland once again was saved cheaply by Curtis Camfer (68).
Curtis Campher then came to the visitors' rescue.
Bairstow's blitz - after Adil Rashid's three for 34 which took him to 150 ODI wickets, the first English spinner to reach the milestone - helped England go 2-0 up on Ireland, rendering Tuesday's meeting a dead rubber. However, Sam Billings (46no) and David Willey (47no) battled through that tricky spell, sharing an unbroken stand of 79, and a four-wicket win was wrapped up with 17.3 overs to spare.
Andrew Balbirnie and Harry Tector looked to settle things down, and saw off both opening bowlers before the former fell to an innocuous delivery from James Vince - who was bowling for the first time in his white ball worldwide career, and for just the seventh time in List A matches.
Campher once again had to make the best of a bad situation and the all-rounder's assured 87-ball knock featured eight fours.
The onslaught continued throughout the powerplay and midway through the eighth over, the Yorkshireman launched McBrine over long off for six to match Morgan's record for England fastest half-century. Campher's introduction with the ball got the breakthrough as he swung one back through James Vince's gate to uproot middle stump.
Bairstow passed 3,000 ODI runs before Josh Little (3-60) impressively dismissed him, Morgan and Ali in quick succession. There is not a single player in the England team in this series, who was part of the team in the 3-match Test series which ended recently with the West Indies. They were down to 78/4 before Sam Billings (67 off 54 deliveries) and skipper Eoin Morgan (36 off 40) shared an unbeaten partnership of 96 runs to take the hosts home.
A six, hooked over deep backward square from Willey off Little, followed by back-to-back boundaries in the next over from Campher signalled the end of the Ireland fightback.
On the basis of wicketkeeper batsman Johnny Bairstow, England defeated Ireland by 4 wickets and also won the second ODI.
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