Three-dimensional (3-D) scaffolds with intrinsic porous structures are desirable in various tissue regeneration applications. In this study, a unique method that combines thermally induced phase separation with a photocrosslinking process was developed for the fabrication of 3-D crosslinked polymer scaffolds with densely interconnected porous structures. Biodegradable poly(propylene fumarate)-co-poly(L-lactic acid) with crosslinkable fumarate bonds were used as the structural polymer material and a dioxane/water binary system was applied for the phase separation. By altering the polymer composition (9, 5 and 3 wt%), different types of scaffolds with distinct morphology, mechanical strength, degradation rate, cell growth and morphology, and extracellular matrix production were fabricated. These crosslinked 3-D porous scaffolds with tunable strength and biological responses show promise for potential applications in regenerative therapies, including bone and neural tissue engineering.