 He remained with the regiment of regulars through the campaigns of 1861 and 1862, then was appointed to an Irish regiment by Governor John Albion Andrew, Colonel of the 28th Massachusetts Volunteer Infantry Regiment, of which he took command on October 18, 1862.His new regiment was attached to Thomas Francis Meagher's Irish Brigade the following November, and with it participated in the fierce fighting in which the Army of the Potomac was subsequently engaged.At its head, Colonel Byrnes charged up the slope of Marye's Heights at the Battle of Fredericksburg, and after it, like the other regiments of the brigade, had been almost wiped out in the sanguinary conflicts at Chancellorsville and Gettysburg, he was sent back to Massachusetts to recruit its ranks during the winter and spring of 1863 and 1864.