The paper presents a Computational Fluid Dynamics (CFD) methodology to model gas-liquid boiling flow in a full scale 5 × 5 rod bundle with spacer grid typical in Pressurized Water Reactor (PWR) fuel rod bundle. The CFD modeling method is developed based on the STAR-CCM+ CFD code, including the Eulerian-Eulerian two-fluid model and the improved wall heat partitioning model. The OECD/NRC PWR Sub-channel and Bundle Tests (PSBT) are used as a numerical benchmark to assess the simulation quantitatively. The simulated geometry is a full scale of 5 × 5 fuel rod bundle with 17 spacers, including 7 mixing vane spacers (MV), 8 simple spacers (SS) and 2 non-mixing vane spacers (NMV). The present simulated results are in good agreement with the experimental results, the average error of the simulated cross-section void fraction is less than 20%. Based on the simulations, the axial distributions of second flow intensity, the rod surface temperature, bulk fluid temperature, and the void fraction are discussed. The results show that the spacer grid structures, especially the mixing vane, play an essential part in spreading the bubbles, reducing the void fraction and the rod surface temperature.