Right-arm pacer Sumon Khan bagged four wickets conceding 31 runs to help Bangladesh deliver a dominating performance.
With this win, Bangladesh sealed the series 3-0 with one match to spare. The last match will be played on March 15.
The first match of the five one-day series had been called off in Chattogram as an Irish player tested positive for Covid-19. He returned negative in a second test.
On Friday, Bangladesh won the toss and opted to bowl first. They restricted the visitors to 182 in 46.2 overs with Mark Adair hitting 40, their highest in the innings.
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Lorcan Tucker (24), Ruhan Pretorius (35) and Graham Hume (29*) were the other batsmen to cross the 20-run mark against a disciplined bowling attack of Bangladesh.
Apart from Sumon, right-arm pacer Mukidul Islam, left-arm spinner Rakibul Hasan and right-arm off-break bowler Saif Hassan took two wickets each.
In reply, Mahmudul Hasan Joy smashed 80 off 135 with eight fours and Towhid Hridoy hit 88 off 97 balls with nine fours.
Mahmudul and Towhid added 176 runs in the third wicket stand after losing two early wickets just in 10 runs.
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For Ireland, Peter Chase took two wickets.
The fifth match of the one-day series will take place at Sher-e-Bangla National Cricket Stadium.
After the one-day series, both teams will lock horn the two-match T20 series. The first match will take place on March 17 while the second will be played on March 18 at the same venue.