Equal channel angular extrusion (ECAE) is a relatively new technique to produce ultrafine-grained materials by severe plastic deformation. Its efficiency of grain refinement varies with the processing route, i.e. the billet rotation () about its longitudinal axis between successive passes. The influence of processing route can not be fully explained by existing theories that consider only the macroscopic deformation features. In this study, the mesoscopic deformation behavior during multi-pass ECAE of face-centered cubic (FCC) metals was simulated using a visco-plasticity self-consistent (VPSC) polycrystal model and assuming simple shear deformation in each pass. It is shown that the slip activities vary significantly at the transitions between successive passes, depending on the die angle and processing route. The efficiencies of grain refinement in the different cases can be well correlated to the contribution of slip systems newly activated in a subsequent pass. The grain refinement is more efficient when such contributions are higher, such as in route B ( = 90) with a 90 die or route A ( = 0) with a 120 die. These crystal plasticity simulations provide insights into the efficiency of grain refinement during severe plastic deformation with strain path changes.