In this work, a comparative investigation of chaotic flow behavior inside multi-layer crossing channels was numerically carried out to select suitable micromixers. New micromixers were proposed and compared with an efficient passive mixer called a Two-Layer Crossing Channel Micromixer (TLCCM), which was investigated recently. The computational evaluation was a concern to the mixing enhancement and kinematic measurements, such as vorticity, deformation, stretching, and folding rates for various low Reynolds number regimes. The 3D continuity, momentum, and species transport equations were solved by a Fluent ANSYS CFD code. For various cases of fluid regimes (0.1 to 25 values of Reynolds number), the new configuration displayed a mixing enhancement of 40%–60% relative to that obtained in the older TLCCM in terms of kinematic measurement, which was studied recently. The results revealed that all proposed micromixers have a strong secondary flow, which significantly enhances the fluid kinematic performances at low Reynolds numbers. The visualization of mass fraction and path-lines presents that the TLCCM configuration is inefficient at low Reynolds numbers, while the new designs exhibit rapid mixing with lower pressure losses. Thus, it can be used to enhance the homogenization in several microfluidic systems.