A multi-dose injection system is disclosed that allows for vacuum-assisted removal of air from an interconnected tubing set and syringes and subsequent filling with fluid. The injection system may include a bulk fluid container holder module operable to hold one or more bottles of fluid for administration to a patient. The holder module may include a vacuum source that is selectively fluidly interconnectable to the tubing set. Air may be removed from the tubing set and syringes by fluidly interconnecting the vacuum source to the tubing set. Then the vacuum source may be fluidly isolated from the tubing set and the bottles fluidly interconnected to the tubing set, thereby allowing fluid from the bottles to fill the at least partially evacuated tubing set and syringes.