Be like Joe Achievement
Be like Joe50
Banked a 300-hit combo
There's a good place to get this on the "Road to Victory" stage. You'll need your Shotgun upgrades at least through the clip size upgrades, as well as have a full clip. Also you'll need ammo for the SMG. When you approach the bathroom for the "Spawn more Deadpool-lords" achievement, stealth kill the normal enemies and let the shield generator enemy go into the bathroom. Stealth kill another normal enemy and there will be a bigger enemy. Get his attention, and lure him into the bathroom with the shield generator enemy. Exit the bathroom and the larger enemy will tend to get stuck, and the shield generator enemy will be in there with him giving him a shield to slow his damage. When he gets stuck, kill the 2 random enemies that are near you and stand behind a pole facing the stuck enemy. Unload all your shotgun rounds into him and you'll be around 250 combo. Switch to your SMG and unload on him until you get to 300. I was able to do this on Veteran difficulty, after having purchased all upgrades. Just try not to shoot the enemy in the head or he'll die too quickly.
Here's a video showing the above mentioned method. Thank you VVh1pCr3am for the video.
Alternate method. Credit goes to hayabusaDGO.