Colchester United U23s lost the second game of their Premier League Cup campaign on Saturday, as they took on Fulham at Craven Cottage.
The U's started strongly, but fell behind after ten minutes, when Thompson fired home from close range past Callum Coulter.
The Cottagers made it 2-0 just before the half hour mark. O'Riley slid through a pass to Atkinson, who in turn set up Santo-Clase to make it 2-0.
Sims set up Forino to head towards goal, only for Ashby-Hammond to save and keep the home side's advantage.
And two became three when O'Riley made it 3-0 as he scored on the rebound to extend the lead on the stroke of half time.
O'Riley got his second and Fulham's fourth five minutes after the break when he struck home a free kick into the bottom corner.
And he completed his hat-trick with fifteen minutes to go with a chipped effort over Coulter.
It made it two wins from two for the home side in this year's cup competition, whilst the U's have lost both to date.