A three-dimensional computational fluid dynamics (CFD) model coupled with reaction kinetics and transport processes is established to investigate the effects of cooling water velocity, tube layer spacing and inter-tube spacing on temperature distribution, pressure drop and CO2 conversion. The results show that, when the flow rate of cooling water is increased from 0.2 m/s to 1.8 m/s, the maximum temperature in the reaction zone is decreased by 4.01 ℃, but the CO2 conversion rate is decreased from 26% to 24.14% due to kinetic inhibition. CO2 conversion can be increased to 31.22% by increasing layer spacing (5-30 cm), but the hot spot temperature is increased by 39.18 ℃. The conversion rate is slightly increased (24.54%-26.57%) by the expansion of tube spacing (30-60 mm)through reducing the heat transfer efficiency. The synergistic mechanism of flow-heat-transfer reaction is revealed, and the gradient layer spacing design is proposed to balance the demand of heat transfer and the optimization of reaction kinetics.