<p>The rapid progress of 3D printing technology has substantially influenced the field of microfluidic research and its diverse applications owing to its remarkable ability to create intricate structures and accelerate the prototyping process. However, 3D printing-based microfluidics still faces several technological challenges, such as the need for expensive high-resolution 3D printers to fabricate intricate microstructures, the limited chemical resistance of commercial 3D printing resins, and the complexities of reusing 3D-printed microfluidic devices. Therefore, we proposed an alternative method for the simple and convenient fabrication of microfluidic devices with high chemical resistance using a typical polytetrafluoroethylene (PTFE) tube. First, a curved serpentine micromixer was fabricated by integrating a flexible PTFE tube with a 3D-printed guide frame that could be easily inserted into it. Subsequently, the mixing efficiency was assessed by varying the inner diameter and curve angle of the tube using both experimental and numerical methods. Furthermore, by changing a 3D-printed guide frame with pinched zones, where the cross-sectional area of the channel is periodically altered, it was demonstrated that the induced chaotic advection at the pinched zones enhances the mixing efficiency. Finally, the chemical resistance tests for various chemical solvents established the applicability of the suggested microfluidic devices to academic and industrial applications that require high chemical resistance such as biochemical synthesis and pharmaceutical manufacturing.</p>